FGL1 is a secreted protein mainly expressed in liver and its expression is further enhanced following acute liver injury. FGL1 null mice have multiple metabolic abnormalities and are more prone to develop hepatocellular carcinoma under certain experimental conditions, suggesting FGL1 has diverse functions in vivo. More recently, FGL1 was found to be highly expressed in human cancer cells and function as an inhibitory ligand for LAG3. Blockade of the FGL1-LAG3 interaction stimulates tumor immunity in mouse models. In addition, a high plasma FGL1 level in human cancer patients is associated with a poor prognosis and resistance to anti-PD-1/PD-L1 immunotherapy.
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